Ophthalmic and otorhinolaryngological device materials containing an alkyl ethoxylate

ABSTRACT

Disclosed are soft, high refractive index, acrylic device materials. The materials contain a functionalized alkyl ethoxylate to reduce glistenings.

This application claims priority to U.S. Provisional Application, U.S.Ser. No. 60/976,969 filed Oct. 2, 2007.

FIELD OF THE INVENTION

This invention is directed to improved ophthalmic andotorhinolaryngological device materials. In particular, this inventionrelates to soft, high refractive index acrylic device materials thathave improved glistening resistance.

BACKGROUND OF THE INVENTION

With the recent advances in small-incision cataract surgery, increasedemphasis has been placed on developing soft, foldable materials suitablefor use in artificial lenses. In general, these materials fall into oneof three categories: hydrogels, silicones, and acrylics.

In general, hydrogel materials have a relatively low refractive index,making them less desirable than other materials because of the thickerlens optic necessary to achieve a given refractive power. Conventionalsilicone materials generally have a higher refractive index thanhydrogels, but tend to unfold explosively after being placed in the eyein a folded position. Explosive unfolding can potentially damage thecorneal endothelium and/or rupture the natural lens capsule. Acrylicmaterials are desirable because they typically have a high refractiveindex and unfold more slowly or controllably than conventional siliconematerials.

U.S. Pat. No. 5,290,892 discloses high refractive index, acrylicmaterials suitable for use as an intraocular lens (“IOL”) material.These acrylic materials contain, as principal components, two arylacrylic monomers. The IOLs made of these acrylic materials can be rolledor folded for insertion through small incisions.

U.S. Pat. No. 5,331,073 also discloses soft acrylic IOL materials. Thesematerials contain as principal components, two acrylic monomers whichare defined by the properties of their respective homopolymers. Thefirst monomer is defined as one in which its homopolymer has arefractive index of at least about 1.50. The second monomer is definedas one in which its homopolymer has a glass transition temperature lessthan about 22° C. These IOL materials also contain a cross-linkingcomponent. Additionally, these materials may optionally contain a fourthconstituent, different from the first three constituents, which isderived from a hydrophilic monomer. These materials preferably have atotal of less than about 15% by weight of a hydrophilic component.

U.S. Pat. No. 5,693,095 discloses foldable, high refractive indexophthalmic lens materials containing at least about 90 wt. % of only twoprincipal components: one aryl acrylic hydrophobic monomer and onehydrophilic monomer. The aryl acrylic hydrophobic monomer has theformula

wherein: X is H or CH₃;

-   -   m is 0-6;    -   Y is nothing, O, S, or NR, wherein R is H, CH₃, C_(n)H_(2n+1)        (n=1-10), iso-OC₃H₇, C₆H₅, or CH₂C₆H₅; and    -   Ar is any aromatic ring which can be unsubstituted or        substituted with CH₃, C₂H₅, n-C₃H₇, iso-C₃H₇, OCH₃, C₆H₁₁, Cl,        Br, C₆H₅, or CH₂C₆H₅.        The lens materials described in the '095 Patent preferably have        a glass-transition temperature (“T_(g)”) between about −20 and        +25° C.

Flexible intraocular lenses may be folded and inserted through a smallincision. In general, a softer material may be deformed to a greaterextent so that it can be inserted through an increasingly smallerincision. Soft acrylic or methacrylic materials typically do not have anappropriate combination of strength, flexibility and non-tacky surfaceproperties to permit IOLs to be inserted through an incision as small asthat required for silicone IOLs.

Polyethylene glycol (PEG) dimethacrylates are known to improveglistening resistance of hydrophobic acrylic formulations. See, forexample, U.S. Pat. Nos. 5,693,095; 6,528,602; 6,653,422; and 6,353,069.Both the concentration and molecular weight of PEG dimethacrylates havean impact on glistening performance. Generally, use of higher molecularweight PEG dimethacrylates (1000 MW) yield copolymers with improvedglistening performance at low PEG concentrations (10-15 wt %), ascompared to lower molecular weight PEG dimethacrylates (<1000 MW).However, low PEG dimethacrylate concentrations are desirable to maintaina high refractive index copolymer. Addition of PEG dimethacrylates alsotends to decrease the modulus and tensile strength of the resultingcopolymer. Also, higher molecular weight PEG dimethacrylates aregenerally not miscible with hydrophobic acrylic monomers.

SUMMARY OF THE INVENTION

Improved soft, foldable acrylic device materials which are particularlysuited for use as IOLs, but which are also useful as other ophthalmic orotorhinolaryngological devices, such as contact lenses,keratoprostheses, corneal rings or inlays, otological ventilation tubesand nasal implants, have been discovered. These polymeric materialscomprise a functionalized alkyl ethoxylate.

Among other factors, the present invention is based on the finding thatuse of alkyl ethoxylate monomers in acrylic intraocular lensformulations reduces or eliminates temperature-induced glisteningformation in hydrophobic acrylic copolymers. The subject monomers allowsynthesis of glistening resistant, low equilibrium water content, highrefractive index IOLs.

DETAILED DESCRIPTION OF THE INVENTION

Unless indicated otherwise, all component amounts are presented on a %(w/w) basis (“wt. %”).

The device materials of the present invention are copolymers comprisinga) a monofunctional acrylate or methacrylate monomer [1], b) adifunctional acrylate or methacrylate cross-linker [2], and c) afunctinoalized alkyl ethoxylate [3]. The device materials may containmore than one monomer [1], more than one monomer [2], and more than onemonomer [3]. Unless indicated otherwise, references to each ingredientare intended to encompass multiple monomers of the same formula andreferences to amounts are intended to refer to the total amount of allmonomers of each formula.

wherein

-   -   B═O(CH₂)_(n), NH(CH₂)_(n), or NCH₃(CH₂)_(n);    -   R¹═H, CH₃, CH₂CH₃, or CH₂OH;    -   n=0-12;    -   A=C₆H₅ or O(CH₂)_(m)C₆H₅, where the C₆H₅ group is optionally        substituted with —(CH₂)_(n)H, —O(CH₂)_(n)H, —CH(CH₃)₂, —C₆H₅,        —OC₆H₅, —CH₂C₆H₅, F, Cl, Br, or I; and    -   m=0-22;

wherein

-   -   R², R³ independently=H, CH₃, CH₂CH₃, or CH₂OH;    -   W, W′ independently=O(CH₂)_(d), NH(CH₂)_(d), NCH₃(CH₂)_(d),        O(CH₂)_(d)C₆H₄, O(CH₂CH₂O)_(d)CH₂, O(CH₂CH₂CH₂O)_(d)CH₂,        O(CH₂CH₂CH₂CH₂O)_(d)CH₂, or nothing;    -   J=(CH₂)_(a), O(CH₂CH₂O)_(b), O, or nothing, provided that if W        and W′=nothing, then J≠nothing;    -   d=0-12;    -   a=1-12;    -   b=1-24;

wherein:

-   -   n=12, 13, or 14;    -   e=1-100;

-   -   R⁴═H, CH₃, CH₂CH₃, CH₂OH; and

Preferred monomers of formula [1] are those wherein:

-   -   B═O(CH₂)_(n);    -   R¹═H or CH₃;    -   n=1-4; and    -   A=C₆H₅.        Preferred monomers of formula [2] are those wherein:    -   R², R³ independently=H or CH₃;    -   W, W′ independently=O(CH₂)_(d), O(CH₂)_(d)C₆H₄, or nothing;    -   J=O(CH₂CH₂O)_(b) or nothing, provided that if W and W′=nothing,        then J≠nothing;    -   d=0-6; and    -   b=1-10.        Preferred monomers of formula [3] are those wherein:    -   e=8-50;

-   -   R⁴═H or CH₃.        Most preferred monomers of formulas [3] are those wherein    -   n=13;    -   e=15-40;

-   -   R⁴═H or CH₃.        Representative monomers of formula [3] include:

Monomers of formula [1] are known and can be made by known methods. See,for example, U.S. Pat. Nos. 5,331,073 and 5,290,892. Many monomers offormula [1] are commercially available from a variety of sources.Preferred monomers of formula [1] include benzyl methacrylate;2-phenylethyl methacrylate; 3-phenylpropyl methacrylate; 4-phenylbutylmethacrylate; 5-phenylpentyl methacrylate; 2-phenoxyethyl methacrylate;2-(2-phenoxyethoxy)ethyl methacrylate; 2-benzyloxyethyl methacrylate;2-(2-(benzyloxy)ethoxy)ethyl methacrylate; and 3-benzyloxypropylmethacrylate; and their corresponding acrylates.

Monomers of formula [2] are known and can be made by known methods, andare commercially available. Preferred monomers of formula [2] includeethylene glycol dimethacrylate (“EGDMA”); diethylene glycoldimethacrylate; triethylene glycol dimethacrylate; 1,6-hexanedioldimethacrylate; 1,4-butanediol dimethacrylate; 1,4-benzenedimethanoldimethacrylate; and their corresponding acrylates. Most preferred is1,4-butanediol diacrylate.

Monomers of formula [3] can be made by known methods. For example, suchmonomers may be made by esterification reactions involving, for example,the alkyl ethoxylate alcohol and suitable carboxylic acids, acylhalides, or carboxylic acid anhydrides. For example, the alkylethoxylate can be heated with a carboxylic acid or carboxylic acid alkylester in the presence of a catalyst to form the desired ester, withwater or low boiling alcohol as a byproduct which can be removed todrive the reaction to completion. The alkyl ethoxylate can also betreated with an acyl halide in the presence of a base such astriethylamine which serves as a hydrohalide acceptor. The alkylethoxylate can also be treated with a carboxylic acid anhydride in thepresence of a base such as triethylamine or pyridine which catalyzes thereaction and neutralizes the acid formed.

The copolymeric materials of the present invention contain a totalamount of monomer [1] from 75 to 97%, preferably from 80 to 95%, andmost preferably from 80-93%. The difunctional cross-linker [2]concentration is generally present in an amount from 0.5-3%, andpreferably 1-2%.

The materials of the present invention have at least one monomer [3].The total amount of monomer [3] depends on the desired physicalproperties for the device materials. The copolymeric materials of thepresent invention contain a total of at least 1% and can contain as muchas 20% of monomer [3]. Preferably, the copolymeric device materials willcontain from 1 to 15% of monomer [3]. Most preferably, the devicematerials will contain from 1 to 10% of monomer [3].

The copolymeric device material of the present invention optionallycontains one or more ingredients selected from the group consisting of apolymerizable UV absorber and a polymerizable colorant. Preferably, thedevice material of the present invention contains no other ingredientsbesides the monomers of formulas [1] and [2], the monomer [3], and theoptional polymerizable UV absorbers and colorants.

The device material of the present invention optionally containsreactive UV absorbers or reactive colorants. Many reactive UV absorbersare known. A preferred reactive UV absorber is2-(2′-hydroxy-3′-methallyl-5′-methylphenyl)benzotriazole, commerciallyavailable as o-Methallyl Tinuvin P (“oMTP”) from Polysciences, Inc.,Warrington, Pa. UV absorbers are typically present in an amount fromabout 0.1-5%. Suitable reactive blue-light absorbing compounds includethose described in U.S. Pat. No. 5,470,932. Blue-light absorbers aretypically present in an amount from about 0.01-0.5%. When used to makeIOLs, the device materials of the present invention preferably containboth a reactive UV absorber and a reactive colorant.

The device material of the present invention optionally containsreactive UV absorbers or reactive colorants. Many reactive UV absorbersare known. A preferred reactive UV absorber is2-(2′-hydroxy-3′-methallyl-5′-methylphenyl)benzotriazole, commerciallyavailable as o-Methallyl Tinuvin P (“oMTP”) from Polysciences, Inc.,Warrington, Pa. UV absorbers are typically present in an amount fromabout 0.1-5%. Suitable reactive blue-light absorbing compounds includethose described in U.S. Pat. No. 5,470,932. Blue-light absorbers aretypically present in an amount from about 0.01-0.5%. When used to makeIOLs, the device materials of the present invention preferably containboth a reactive UV absorber and a reactive colorant.

In order to form the device material of the present invention, thechosen ingredients [1], [2], and [3], along with any of the optionalingredients, are combined and polymerized using a radical initiator toinitiate polymerization by the action of either heat or radiation. Thedevice material is preferably polymerized in de-gassed polypropylenemolds under nitrogen or in glass molds.

Suitable polymerization initiators include thermal initiators andphotoinitiators. Preferred thermal initiators include peroxyfree-radical initiators, such as t-butyl(peroxy-2-ethyl)hexanoate anddi-(tert-butylcyclohexyl)peroxydicarbonate (commercially available asPerkadoxe 16 from Akzo Chemicals Inc., Chicago, Ill.). Particularly incases where the materials of the present invention do not contain ablue-light absorbing chromophore, preferred photoinitiators includebenzoylphosphine oxide initiators, such as2,4,6-trimethyl-benzoyidiphenyl-phosphine oxide, commercially availableas Lucirin® TPO from BASF Corporation (Charlotte, N.C.). Initiators aretypically present in an amount equal to about 5% or less of the totalformulation weight, and more preferably less than 2% of the totalformulation. As is customary for purposes of calculating componentamounts, the initiator weight is not included in the formulation weight% calculation.

The particular combination of the ingredients described above and theidentity and amount of any additional components are determined by thedesired properties of the finished device material. In a preferredembodiment, the device materials of the present invention are used tomake IOLs having an optic diameter of 5.5 or 6 mm that are designed tobe compressed or stretched and inserted through surgical incision sizesof 2 mm or less. For example, the monomer [3] is combined with at leastone mono-functional acrylate or methacrylate monomer [1] and amultifunctional acrylate or methacrylate cross-linker [2] andcopolymerized using a radical initiator in a suitable lens mold.

The device material preferably has a refractive index in the hydratedstate of at least about 1.50, and more preferably at least about 1.53,as measured by an Abbe' refractometer at 589 nm (Na light source) and25° C. Optics made from materials having a refractive index lower than1.50 are necessarily thicker than optics of the same power which aremade from materials having a higher refractive index. As such, IOLoptics made from materials with comparable mechanical properties and arefractive index lower than about 1.50 generally require relativelylarger incisions for IOL implantation.

The proportions of the monomers to be included in the copolymers of thepresent invention should be chosen so that the copolymer has a glasstransition temperature (T_(g)) not greater than about 37° C., which isnormal human body temperature. Copolymers having glass transitiontemperatures higher than 37° C. are not suitable for use in foldableIOLs; such lenses could only be rolled or folded at temperatures above37° C. and would not unroll or unfold at normal body temperature. It ispreferred to use copolymers having a glass transition temperaturesomewhat below normal body temperature and no greater than normal roomtemperature, e.g., about 20-25° C., in order that IOLs made of suchcopolymers can be rolled or folded conveniently at room temperature.T_(g) is measured by differential scanning calorimetry at 10° C./min.,and is determined at the midpoint of the transition of the heat fluxcurve.

For IOLs and other applications, the materials of the present inventionmust exhibit sufficient strength to allow devices made of them to befolded or manipulated without fracturing. Thus the copolymers of thepresent invention will have an elongation of at least 80%, preferably atleast 100%, and most preferably between 110 and 200%. This propertyindicates that lenses made of such materials generally will not crack,tear or split when folded. Elongation of polymer samples is determinedon dumbbell shaped tension test specimens with a 20 mm total length,length in the grip area of 4.88 mm, overall width of 2.49 mm, 0.833 mmwidth of the narrow section, a fillet radius of 8.83 mm, and a thicknessof 0.9 mm. Testing is performed on samples at ambient conditions usingan Instron Material Tester (Model No. 4442 or equivalent) with a 50Newton load cell. The grip distance is set at 14 mm and a crossheadspeed is set at 500 mm/minute and the sample is pulled until failure.The elongation (strain) is reported as a fraction of the displacement atfailure to the original grip distance. Since the materials to be testedare essentially soft elastomers, loading them into the Instron machinetends to make them buckle. To remove the slack in the material sample apre-load is placed upon the sample. This helps to reduce the slack andprovide a more consistent reading. Once the sample is pre-loaded to adesired value (typically 0.03 to 0.05 N) the strain is set to zero andthe test begun. The modulus is calculated as the instantaneous slope ofthe stress-strain curve at 0% strain (“Young's modulus”), 25% strain(“25% modulus”) and 100% strain (“100% modulus).

IOLs made of the ophthalmic device materials of the present inventionare more resistant to glistenings than other materials. Glistenings aremeasured according to the following test. The presence of glistenings ismeasured by placement of a lens or disk sample into a vial or sealedglass chamber and adding deionized water or a balanced salt solution.The vial or glass chamber is then placed into a water bath preheated to45° C. Samples are to be maintained in the bath for a minimum of 16hours and preferably 24±2 hours. The vial or glass chamber is thencooled to ambient temperature for a minimum of 60 minutes and preferably90±30 minutes. The sample is inspected visually in various on angle oroff angle lighting to evaluate clarity. Visualization of glistenings iscarried out at ambient temperature with a light microscope using amagnification of 50 to 200×. A sample is judged to have many glisteningsif, at 50-200× magnification, there are approximately 50 to 100% as manyglistenings as observed in control samples based on 65 weight % PEA, 30weight % PEMA, 3.2 weight % BDDA, and 1.8 weight % OMTP. Similarly, asample is judged to have few glistenings if there are approximately 10%or more glistenings relative to the quantity observed in controlsamples. A sample is judged to have very few glistenings if there areapproximately 1% or more glistenings relative to a control sample. Asample is judged to be free of glistenings if the number of glisteningsdetected in the eyepiece is zero. A sample is judged to be substantiallyfree of glistenings if, at 50-200× magnification, the number ofglistenings detected in the eyepiece is less than about 2/mm³. It isoften very difficult to detect glistenings, especially at surfaces andedges where more defects and debris have formed, so the sample israstered throughout the entire volume of the lens, varying themagnification levels (50-200×), the aperture iris diaphragm, and thefield conditions (using both bright field and dark field conditions) inan attempt to detect the presence of glistenings.

The copolymers of the present invention preferably have an equilibriumwater content (EWC) of 0.5 to 3 weight %. EWC is measured by placing onerectangular 0.9×10×20 mm slab in a 20 ml scintillation vial filled withdeionized water and subsequently heating in a 35° C. water bath for aminimum of 20 hours and preferably 48±8 hours. The slab is blotted drywith lens paper and the % water content is calculated as follows:

${\% \mspace{14mu} {water}\mspace{14mu} {content}} = {\frac{\left( {{{wet}\mspace{14mu} {weight}} - {{dry}\mspace{14mu} {weight}}} \right)}{{wet}\mspace{14mu} {weight}} \times 100}$

IOLs constructed of the device materials of the present invention can beof any design capable of being stretched or compressed into a smallcross section that can fit through a 2-mm incision. For example, theIOLs can be of what is known as a one-piece or multi-piece design, andcomprise optic and haptic components. The optic is that portion whichserves as the lens and the haptics are attached to the optic and arelike arms that hold the optic in its proper place in the eye. The opticand haptic(s) can be of the same or different material. A multi-piecelens is so called because the optic and the haptic(s) are madeseparately and then the haptics are attached to the optic. In a singlepiece lens, the optic and the haptics are formed out of one piece ofmaterial. Depending on the material, the haptics are then cut, orlathed, out of the material to produce the IOL.

In addition to IOLs, the materials of the present invention are alsosuitable for use as other ophthalmic or otorhinolaryngological devicessuch as contact lenses, keratoprostheses, corneal inlays or rings,otological ventilation tubes and nasal implants.

The invention will be further illustrated by the following examples,which are intended to be illustrative, but not limiting.

The following abbreviations are used throughout the Examples and havethe following meanings.

-   PEA 2-phenylethyl acrylate-   PEMA 2-phenylethyl methacrylate-   BzA benzyl acrylate-   BZMA benzyl methacrylate-   BDDA 1,4-butanediol diacrylate-   AIBN azobisisobutyronitrile-   THF tetrahydrofuran-   AIBN azobisisobutyronitrile-   OMTP    2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-methyl-6-(2-methylallyl)phenol-   TMI 3-isopropenyl-alpha,alpha-dimethylbenzyl isocyanate-   MEHQ methyl hydroquinone or 4-methoxyphenol-   Terg15S3-MA Reacted adduct of Tergitol™ 15-S-3 alkyl ethoxylate and    methacrylic anhydride-   Terg15S7-MA Reacted adduct of Tergitol™ 15-S-7 alkyl ethoxylate and    methacrylic anhydride-   Terg15S30-MA Reacted adduct of Tergitol™ 15-S-30 alkyl ethoxylate    and methacrylic anhydride-   Terg15S40-MA Reacted adduct of Tergitol™ 15-S-40 alkyl ethoxylate    and methacrylic anhydride-   Terg15S3-TMI Reacted adduct of Tergitol™ 15-S-3 alkyl ethoxylate and    TMI-   Terg15S7-TMI Reacted adduct of Tergitol™ 15-S-7 alkyl ethoxylate and    TMI-   Terg15S5-TMI Reacted adduct of Tergitol™ 15-S-15 alkyl ethoxylate    and TMI

EXAMPLE 1

Terg15S30-MA. 50.1 g (34.0 mmol based on OH#=38.0 mg KOH/g) of Tergitol15-S-30 surfactant (Dow/Union Carbide), 15.7 g (102 mmol) methacrylicanhydride (Aldrich, 94%), and 20 mg MEHQ (Sigma-Aldrich) were dissolvedin 120 g anhydrous pyridine (Burdick & Jackson) in a 500 ml round bottomflask equipped with magnetic stirrer and nitrogen inlet. The reactionmixture was heated at 50° C. for 20 hours, poured into 3000 ml diethylether, and subsequently cooled to −20° C. The solvent was decanted andthe solid was recovered by centrifugation. The solid was redissolved inether and the product was recovered as previously described to give 43.8g (80%) of a white waxy solid.

EXAMPLE 2

Terg15S40-MA. 105.0 g (54.7 mmol based on OH#=29.2 mg KOH/g) of Tergitol15-S-40 (Dow/Union Carbide) was dissolved in 300 ml anhydrous pyridine.20 mg MEHQ and 50 mg dibutyltin dilaurate (Aldrich, Milwaukee, Wis.)were added followed by 17.6 g methacrylic anhydride (Alfa Aesar, 94%).The reaction mixture was heated at 60° C. for 15 hours and the solidisolated by precipitation in diethyl ether 3 times as described in Ex. 1to give 90 g (82 %).

EXAMPLE 3 Lens Materials

The reaction components listed in Tables 1-4, except for AIBN, weremixed together with stirring or shaking for at least 30 minutes at 23°C., until all components were dissolved. The AIBN was subsequently addedand the reaction mixture was stirred for an additional 5 minutes orlonger, until the initiator was dissolved. The reactive components arereported in weight %.

The reactive components were purged for approximately 15 minutes usingN₂ and placed inside a low humidity N₂ purged glove box.

The reactive components were syringed or pipetted onto cleanpolypropylene mold halves containing 1×10×20 mm rectangular wells andcovered with the complementary flat polypropylene mold halves. The moldhalves were compressed using binder clips and the mixtures were heatramped from ambient temperature to 70° C. in 15 minutes, and then curedat 70° C. for 1 hour and 110° C. for 2 hours using a Yamato DKN400constant temperature oven. The molds were allowed to cool to roomtemperature. The top mold halves were removed and the rectangularpolymer slabs were removed from the wells with tweezers and placedindividually in 38×8 mm Histo Plas tissue processing capsules (Bio PlasInc., San Rafael, Calif.). The slabs were extracted in acetone for aminimum of 8 hours and then air dried at ambient temperature for 20hours, followed by high vacuum (˜0.1 mm Hg) at ambient temperature for20 hours, and high vacuum at 70° C. for 20 hours.

TABLE 1 Example % (w/w) Component 3A 3B 3C 3D 3E 3F Ex 1 5.0 5.1 5.1 5.05.0 6.0 BzA 87.0 82.0 81.2 79.8 90.0 92.0 BzMA 6.0 11.4 12.2 13.6 3.0 0BDDA 2.0 1.6 1.5 1.6 2.0 2.0 AIBN 0.52 0.50 0.53 0.56 0.50 0.52

TABLE 2 Example % (w/w) Component 3G 3H 3I 3J 3K 3L Ex 1 5.0 5.0 5.0 5.05.0 6.1 PEA 50.0 54.1 58.0 51.3 49.9 48.4 PEMA 43.6 39.5 35.5 42.2 44.043.7 BDDA 1.5 1.4 1.6 1.5 1.1 1.8 AIBN 0.50 0.52 0.48 0.50 0.49 0.55

TABLE 3 Example % (w/w) Component 3M 3N 3O 3P 3Q 3R Ex 1 5.0 8.1 5.0 6.16.1 5.9 PEA 63.6 61.5 63.9 62.7 63.1 63.2 PEMA 9.0 28.6 14.8 7.4 7.111.7 BzMA 20.5 0 14.6 21.9 21.9 17.4 BDDA 1.9 1.8 1.8 2.0 1.8 1.7 AIBN0.48 0.48 0.56 0.52 0.51 0.57

TABLE 4 Example % (w/w) Component 3S 3T 3U 3V 3W 3X Ex 1 0 5.0 5.0 0 06.1 Ex 2 6.1 0 0 6.1 6.1 0 PEA 62.9 52.0 0 48.0 33.4 62.9 PEMA 7.3 41.413.7 43.9 58.5 7.3 BzA 0 0 79.8 0 0 0 BzMA 21.8 0 0 0 0 21.8 BDDA 1.81.5 1.5 2.0 2.0 2.0 AIBN 0.49 0.52 0.50 0.53 0.55 0.51The % extractables were calculated as follows:

${\% \mspace{14mu} {extractables}} = {\frac{\begin{pmatrix}{{{non}\text{-}{extracted}\mspace{14mu} {weight}} -} \\{{extracted}\mspace{14mu} {weight}}\end{pmatrix}}{{non}\text{-}{extracted}\mspace{14mu} {weight}} \times 100}$

The equilibrium water content (EWC) was measured by placing a slab in 20ml deionized water in a scintillation vial and heating in a 35° C. waterbath for a minimum of 20 hours. The slab was blotted dry with lens paperand the % water content was calculated as follows:

${\% \mspace{14mu} {water}\mspace{14mu} {content}} = {\frac{\left( {{{wet}\mspace{14mu} {weight}} - {{dry}\mspace{14mu} {weight}}} \right)}{{wet}\mspace{14mu} {weight}} \times 100}$

Refractive index values of the hydrated samples were measured using aBausch & Lomb refractometer (catalog #33.46.10) at 35° C.

The extent of glistening formation was evaluated by equilibratingsamples in water at 45° C. followed by cooling to 23° C. and subsequentexamination using a light microscope. Samples were first placed in 20 mlscintillation vials containing deionized water and heated at 45° C. fora minimum of 20 hours. The entire cross section (˜200 mm²) of sampleswas examined for glistening formation approximately 1 to 2 hours aftercooling to ambient temperature using an Olympus BX60 microscope equippedwith 10× and 20× objectives. The samples were also visually inspectedfor haze after the AT test and all samples remained clear.

The refractive index (R.I.), % extractables, equilibrium water content(EWC), and glistening results are shown in Table 5.

TABLE 5 Relative % Glistening Ex. # R.I. Extractables EWC Concentration3A 1.554 2.2 — Very few 3B 1.558 2.6 0.8 0 3C 1.556 2.5 0.8 0 3D 1.5593.1 0.8 0 3E 1.553 2.8 0.5 0 3F 1.553 3.8 1.0 Very few 3G 1.547 1.6 0.6Very few 3H 1.547 1.7 0.9 0 3I 1.547 1.8 0.6 0 3J 1.547 1.8 0.9 0 3K1.547 1.9 0.8 0 3L 1.546 1.6 1.0 0 3M 1.547 0.8 0.7 0 3N 1.542 2.3 2.0 03O 1.547 1.8 1.0 Very few 3P 1.548 2.5 1.1 Very few 3Q 1.547 2.6 1.1Very few 3R 1.546 1.8 1.0 Very few 3S 1.545 1.7 1.9 Very few 3T 1.5501.9 0.6 Very few 3U 1.553 2.2 0.8 0 3V 1.547 1.5 1.9 Very few 3W 1.5491.4 1.5 Very few 3X 1.550 1.9 1.2 Very few

The results of Examples 3A through 3X show that the reaction mixturecomponents and their amounts may be varied. All materials were clear andshowed low haze.

The refractive index (R.I.) values of Examples 3A through 3F and 3Uwhich contain BzA were higher than 1.55, whereas R.I. values of Examples3G through 3X, excluding 3U, which contain PEA were slightly lower andbetween 1.54 and 1.55.

The equilibrium water contents (EWCs) were generally 1% or less when 5weight percent of the functionalized hydrophilic component was added.The EWC was as high as 2% in Example 3N which contained 8 weight percentof the functionalized hydrophilic component.

In all examples, zero to very few glistenings could be observed perentire slab using 10× or 20× magnification objectives (such that theoverall magnification was 50-200×). Glistening sightings were rare andobserved mainly along edges.

The materials from Examples 3A through 3X were analyzed to determinetheir tensile properties. The results are shown in Table 6, below.

TABLE 6 25% 100% Stress at Young's Secant Secant Break Strain at ModulusModulus Modulus Ex. # (MPa) Break (%) (MPa) (MPa) (MPa) 3A 9.2 163 37.86.6 3.6 3B 9.8 211 55.1 8.9 3.5 3C 10.4 216 61.5 9.4 3.6 3D 10.4 151 11915.2 6.4 3E 9.0 168 27.5 5.3 3.2 3F 8.1 163 17.8 3.8 2.5 3G 7.7 156 59.59.9 4.3 3H 7.2 170 34.6 6.3 3.1 3I 6.3 153 24.2 5.0 2.9 3J 6.1 147 27.05.3 2.9 3K 7.6 200 53.8 9.1 3.4 3L 9.2 145 48.1 9.2 4.8 3M 7.4 140 27.35.5 3.5 3N 4.4 140 7.4 2.4 1.9 3O 8.2 160 20.1 4.5 2.8 3P 6.6 136 24.95.3 3.5 3Q 7.3 151 22.3 4.9 3.0 3R 7.1 153 19.6 4.3 2.7 3S 6.7 152 16.23.9 2.6 3T 7.1 145 20.0 4.6 3.1 3U 8.7 140 46.5 9.3 4.8 3V 8.3 137 37.27.6 4.5 3W 9.5 91 113 24.4 — 3X 6.3 137 19.8 4.5 3.2

EXAMPLE 4

Terg15S3-MA. 10.0 g (28.3 mmol based on OH#=158.6 mg KOH/g) of Tergitol15-S-3 (Dow/Union Carbide) was dissolved in 100 ml anhydrous pyridine.20 mg MEHQ and 50 μl of 0.3 M dibutyltin dilaurate (Aldrich, Milwaukee,Wis.) in toluene were added followed by 8.7 g (56.4 mmol) methacrylicanhydride (Alfa Aesar, 94%). The reaction mixture was heated at 50° C.for 20 hours and the resultant liquid was dissolved in 500 ml methylenechloride and washed with 0.2 N HCl (3×500 ml), 0.2 M NaHCO₃ (3×500 ml),brine, and water. The organic layer was dried with anhydrous Na₂SO₄ andthe product was isolated as a slightly yellow liquid (8 g, 67% yield).

EXAMPLE 5

Terg15S7-MA. 10.0 g (18.55 mmol based on OH#=104.1 mg KOH/g) of Tergitol15-S-3 (Dow/Union Carbide) was dissolved in 100 ml anhydrous pyridine.20 mg MEHQ and 50 μl of 0.3 M dibutyltin dilaurate (Aldrich, Milwaukee,Wis.) in toluene were added followed by 7.2 g (47 mmol) methacrylicanhydride (Alfa Aesar, 94%). The reaction mixture was heated at 50° C.for 20 hours and the resultant liquid was dissolved in 500 ml methylenechloride and washed with 0.2 N HCl (3×500 ml), 0.2 M NaHCO3 (3×500 ml),brine, and water. The organic layer was dried with anhydrous Na2SO4 andthe product was isolated as a slightly yellow liquid (5 g, 44% yield).

EXAMPLE 6

Terg15S3-TMI. 4.97 g (14.0 mmol based on OH#=158.6 mg KOH/g) of Tergitol15-S-3 (Dow/Union Carbide) was dissolved in 30 ml chloroform. 20 mg MEHQand 20 mg dibutyltin dilaurate (Aldrich, Milwaukee, Wis.) were addedfollowed by 2.96 g (14.7 mmol) 3-isopropenyl-alpha,alpha-dimethylbenzylisocyanate (Aldrich). The reaction mixture was heated at 60° C. for 16hours and the resultant liquid was dissolved in 300 ml methylenechloride and washed with 0.2 N HCl (3×500 ml), 0.2 M NaHCO₃ (3×300 ml),brine, and water. The organic layer was dried with anhydrous Na₂SO₄ andthe solvent removed by rotary evaporation to yield a slightly yellowliquid (5 g, 64%). Data on 13117-27

EXAMPLE 7

Terg15S7-TMI. 4.97 g (9.22 mmol based on OH#=104.1 mg KOH/g) of Tergitol15-S-7 (Dow/Union Carbide) was dissolved in 30 ml chloroform. 20 mg MEHQand 20 mg dibutyltin dilaurate (Aldrich, Milwaukee, Wis.) were addedfollowed by 2.06 g (10.2 mmol) 3-isopropenyl-alpha,alpha-dimethylbenzylisocyanate (Aldrich). The reaction mixture was heated at 60° C. for 16hours and the resultant liquid was dissolved in 300 ml methylenechloride and washed with 0.2 N HCl (3×500 ml), 0.2 M NaHCO₃ (3×300 ml),brine, and water. The organic layer was dried with anhydrous Na₂SO₄ andthe solvent removed by rotary evaporation to yield a slightly yellowliquid (3.5 g, 51%). Data on 13117-28

EXAMPLE 8

Terg15S15-TMI. 5.0 g (5.7 mmol based on OH#=64.4 mg KOH/g) of Tergitol15-S-15 (Dow/Union Carbide) was dissolved in THF (100 ml). 20 mg MEHQand 20 mg dibutyltin dilaurate (Aldrich, Milwaukee, Wis.) were addedfollowed by 1.13 g (5.61 mmol) 3-isopropenyl-alpha,alpha-dimethylbenzylisocyanate (Aldrich). The reaction mixture was heated at 60° C. for 16hours and the solvent removed by rotary evaporation to yield a slightlyyellow liquid. Data on 13117-29

EXAMPLE 9 Lens Materials Using Lower Molecular Weight Alkyl Ethoxylates

The reaction components listed in Table 7 were mixed together and curedas previously described. Higher concentrations of alkyl ethoxylate wereused as compared to Tables 1 through 4 due to the relatively lowermolecular weight and lower PEG contents of alkyl ethoxylates in Examples4 through 8. This enables the incorporation of greater amounts of thefunctionalized alkyl ethoxylates while still maintaining equilibriumwater contents of approximately 1.5% or less as shown in Table 8.

The results of Examples 9C through 9G which contain between 3 to 12weight % of Terg15S15-TMI, as shown in Table 7, show that decreasing thealkyl ethoxylate content below approximately 8 weight % results in theappearance of glistenings and noticeable haze. The results of Examples9A show that a relatively high incorporation of approximately 15 weight% Terg15S3-TMI, the lowest molecular weight alkyl ethoxylate, results inclear samples but does not eliminate glistening formation.

TABLE 7 Example (% w/w) Component 9A 9B 9C 9D 9E 9F 9G Ex 6 14.7 0 0 0 00 0 Ex 7 0 13.2 0 0 0 0 0 Ex 8 0 0 11.8 9.9 7.8 5.7 3.2 PEA 55.3 56.357.1 58.5 59.9 61.3 63.0 PEMA 25.5 26.0 26.4 27.0 27.7 28.3 29.1 BDDA3.0 3.0 3.1 2.9 3.0 3.0 3.1 OMTP 1.5 1.6 1.6 1.6 1.7 1.7 1.7 AIBN 0.430.47 0.44 0.45 0.47 0.48 0.51

TABLE 8 Sample Appearance Post Relative % Glistening glistening Ex. #R.I. Extractables EWC Test concentration 9A 1.542 2.7 0.5 clear many 9B1.543 2.8 0.7 clear few 9C 1.546 6.1 0.9 clear 0 9D 1.545 5.4 0.8 clear0 9E 1.550 4.0 0.6 slightly hazy — 9F 1.549 4.1 0.6 slightly hazy many9G 1.551 2.5 0.9 slightly hazy many

This invention has been described by reference to certain preferredembodiments; however, it should be understood that it may be embodied inother specific forms or variations thereof without departing from itsspecial or essential characteristics. The embodiments described aboveare therefore considered to be illustrative in all respects and notrestrictive, the scope of the invention being indicated by the appendedclaims rather than by the foregoing description.

1. A polymeric ophthalmic or otorhinolaryngological device materialcomprising a) 75 to 97% (w/w) of a monofunctional acrylate ormethacrylate monomer of formula [1]:

wherein B═O(CH₂)_(n), NH(CH₂)_(n), or NCH₃(CH₂)_(n); R¹═H, CH₃, CH₂CH₃,or CH₂OH; n=0-12; A=C₆H₅ or O(CH₂)_(m)C₆H₅, where the C₆H₅ group isoptionally substituted with —(CH₂)_(n)H, —O(CH₂)_(n)H, —CH(CH₃)₂, —C₆H₅,—OC₆H₅, —CH₂C₆H₅, F, Cl, Br, or I; and m=0-22; b) a difunctionalacrylate or methacrylate cross-linking monomer of formula [2]:

wherein R², R³ independently=H, CH₃, CH₂CH₃, or CH₂OH; W, W′independently=O(CH₂)_(d), NH(CH₂)_(d), NCH₃(CH₂)_(d), O(CH₂)_(d)C₆H₄,O(CH₂CH₂O)_(d)CH₂, O(CH₂CH₂CH₂O)_(d)CH₂, O(CH₂CH₂CH₂CH₂O)_(d)CH₂, ornothing; J=(CH₂)_(a), O(CH₂CH₂O)_(b), O, or nothing, provided that if Wand W′=nothing, then J≠nothing; d=0-12; a=1-12; and b=1-24; and c) 1 to20% (w/w) of an alkyl ethoxylate monomer of formula [3]:

wherein: n=12, 13, or 14; e=1-100;

R⁴═H, CH₃, CH₂CH₃, CH₂OH; and


2. The polymeric device material of claim 1 wherein B═O(CH₂)_(n); R¹═Hor CH₃; n=1-4; and A=C₆H₅.
 3. The polymeric device material of claim 1wherein R², R³ independently=H or CH₃; W, W′ independently=O(CH₂)_(d),O(CH₂)_(d)C₆H₄, or nothing; J=O(CH₂CH₂O)_(b) or nothing, provided thatif W and W′=nothing, then J≠nothing; d=0-6; and b=1-10.
 4. The polymericdevice material of claim 1 wherein: n=12, 13, or 14; e=8-50;

R⁴═H or CH₃.
 5. The polymeric device material of claim 4 wherein: n=13;e=15-40;

R⁴═H or CH₃.
 6. The polymeric device material of claim 1 wherein themonomer of formula [1] is selected from the group consisting of benzylmethacrylate; 2-phenylethyl methacrylate; 3-phenylpropyl methacrylate;4-phenylbutyl methacrylate; 5-phenylpentyl methacrylate; 2-phenoxyethylmethacrylate; 2-(2-phenoxyethoxy)ethyl methacrylate; 2-benzyloxyethylmethacrylate; 2-(2-(benzyloxy)ethoxy)ethyl methacrylate;3-benzyloxypropyl methacrylate; benzyl acrylate; 2-phenylethyl acrylate;3-phenylpropyl acrylate; 4-phenylbutyl acrylate; 5-phenylpentylacrylate; 2-phenoxyethyl acrylate; 2-(2-phenoxyethoxy)ethyl acrylate;2-benzyloxyethyl acrylate; 2-(2-(benzyloxy)ethoxy)ethyl acrylate; and3-benzyloxypropyl acrylate.
 7. The polymeric device material of claim 1wherein the monomer of formula [2] is selected from the group consistingof ethylene glycol dimethacrylate; diethylene glycol dimethacrylate;triethylene glycol dimethacrylate; 1,6-hexanediol dimethacrylate;1,4-butanediol dimethacrylate; 1,4-benzenedimethanol dimethacrylate;ethylene glycol diacrylate; diethylene glycol diacrylate; triethyleneglycol diacrylate; 1,6-hexanediol diacrylate; 1,4-butanediol diacrylate;and 1,4-benzenedimethanol diacrylate.
 8. The polymeric device materialof claim 1 wherein the amount of monomer [1] is 80 to 95% (w/w).
 9. Thepolymeric device material of claim 1 wherein the amount of monomer [2]is 0.5 to 3% (w/w).
 10. The polymeric device material of claim 1 whereinthe amount of monomer [3] is 1 to 15% (w/w).
 11. The polymeric devicematerial of claim 10 wherein the amount of monomer [3] is 1 to 10%(w/w).
 12. The polymeric device material of claim 1 further comprisingan ingredient selected from the group consisting of a polymerizable UVabsorbers and a polymerizable colorants.
 13. The polymeric devicematerial of claim 12 comprising 0.1-5% (w/w) of a polymerizable UVabsorber and 0.01-0.5% (w/w) of a polymerizable colorant.
 14. Anophthalmic or otorhinolaryngological device comprising the devicematerial of claim 1 wherein the ophthalmic or otorhinolaryngologicaldevice is selected from the group consisting of intraocular lenses;contact lenses; keratoprostheses; corneal inlays or rings; otologicalventilation tubes; and nasal implants.
 15. The ophthalmic orotorhinolaryngological device of claim 14 wherein the ophthalmic orotorhinolaryngological device is an intraocular lens.